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Proteins. 2013 Jul 10. doi: 10.1002/prot.24356. [Epub ahead of print]
Community-wide evaluation of methods for predicting the effect of mutations on protein-protein interactions.
Moretti R, Fleishman SJ, Agius R, Torchala M, Bates PA, Kastritis PL, Rodrigues JP, Trellet M, Bonvin AM, Cui M, Rooman M, Gillis D, Dehouck Y, Moal I, Romero-Durana M, Perez-Cano L, Pallara C, Jimenez B, Fernandez-Recio J, Flores S, Pacella M, Kilambi KP, Gray JJ, Popov P, Grudinin S, Esquivel-Rodr?guez J, Kihara D, Zhao N, Korkin D, Zhu X, Demerdash ON, Mitchell JC, Kanamori E, Tsuchiya Y, Nakamura H, Lee H, Park H, Seok C, Sarmiento J, Liang S, Teraguchi S, Standley DM, Shimoyama H, Terashi G, Takeda-Shitaka M, Iwadate M, Umeyama H, Beglov D, Hall DR, Kozakov D, Vajda S, Pierce BG, Hwang H, Vreven T, Weng Z, Huang Y, Li H, Yang X, Ji X, Liu S, Xiao Y, Zacharias M, Qin S, Zhou HX, Huang SY, Zou X, Velankar S, Janin J, Wodak SJ, Baker D.
Source
Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Abstract
Community-wide blind prediction experiments such as CAPRI and CASP provide an objective measure of the current state of predictive methodology. Here we describe a community-wide assessment of methods to predict the effects of mutations on protein-protein interactions. Twenty-two groups predicted the effects of comprehensive saturation mutagenesis for two designed influenza hemagglutinin binders and the results were compared with experimental yeast display enrichment data obtained using deep sequencing. The most successful methods explicitly considered the effects of mutation on monomer stability in addition to binding affinity, carried out explicit side chain sampling and backbone relaxation, and evaluated packing, electrostatic and solvation effects, and correctly identified around a third of the beneficial mutations. Much room for improvement remains for even the best techniques, and large-scale fitness landscapes should continue to provide an excellent test bed for continued evaluation of methodological improvement. ? Proteins 2013;. ? 2013 Wiley Periodicals, Inc.
Copyright ? 2013 Wiley Periodicals, Inc., a Wiley company.
KEYWORDS:
CAPRI, binding, deep mutational scanning, hemagglutinin, yeast display
PMID:
23843247
[PubMed - as supplied by publisher]
Community-wide evaluation of methods for predicting the effect of mutations on protein-protein interactions.
Moretti R, Fleishman SJ, Agius R, Torchala M, Bates PA, Kastritis PL, Rodrigues JP, Trellet M, Bonvin AM, Cui M, Rooman M, Gillis D, Dehouck Y, Moal I, Romero-Durana M, Perez-Cano L, Pallara C, Jimenez B, Fernandez-Recio J, Flores S, Pacella M, Kilambi KP, Gray JJ, Popov P, Grudinin S, Esquivel-Rodr?guez J, Kihara D, Zhao N, Korkin D, Zhu X, Demerdash ON, Mitchell JC, Kanamori E, Tsuchiya Y, Nakamura H, Lee H, Park H, Seok C, Sarmiento J, Liang S, Teraguchi S, Standley DM, Shimoyama H, Terashi G, Takeda-Shitaka M, Iwadate M, Umeyama H, Beglov D, Hall DR, Kozakov D, Vajda S, Pierce BG, Hwang H, Vreven T, Weng Z, Huang Y, Li H, Yang X, Ji X, Liu S, Xiao Y, Zacharias M, Qin S, Zhou HX, Huang SY, Zou X, Velankar S, Janin J, Wodak SJ, Baker D.
Source
Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Abstract
Community-wide blind prediction experiments such as CAPRI and CASP provide an objective measure of the current state of predictive methodology. Here we describe a community-wide assessment of methods to predict the effects of mutations on protein-protein interactions. Twenty-two groups predicted the effects of comprehensive saturation mutagenesis for two designed influenza hemagglutinin binders and the results were compared with experimental yeast display enrichment data obtained using deep sequencing. The most successful methods explicitly considered the effects of mutation on monomer stability in addition to binding affinity, carried out explicit side chain sampling and backbone relaxation, and evaluated packing, electrostatic and solvation effects, and correctly identified around a third of the beneficial mutations. Much room for improvement remains for even the best techniques, and large-scale fitness landscapes should continue to provide an excellent test bed for continued evaluation of methodological improvement. ? Proteins 2013;. ? 2013 Wiley Periodicals, Inc.
Copyright ? 2013 Wiley Periodicals, Inc., a Wiley company.
KEYWORDS:
CAPRI, binding, deep mutational scanning, hemagglutinin, yeast display
PMID:
23843247
[PubMed - as supplied by publisher]
